Healthcare Use during the Last Six Months of Life in Patients with Advanced Breast Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Data Collection
2.3. Definitions
2.4. Outcomes
2.5. Statistics
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Torre, L.A.; Siegel, R.L.; Ward, E.M.; Jemal, A. Global cancer incidence and mortality rates and trends—An update. Cancer Epidemiol. Biomark. Prev. 2016, 25, 16–27. [Google Scholar] [CrossRef] [Green Version]
- Cinausero, M.; Gerratana, L.; de Carlo, E.; Iacono, D.; Bonotto, M.; Fanotto, V.; Buoro, V.; Basile, D.; Vitale, M.G.; Rihawi, K.; et al. Determinants of last-line treatment in metastatic breast cancer. Clin. Breast Cancer 2018, 18, 205–213. [Google Scholar] [CrossRef] [PubMed]
- Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021, 71, 209–249. [Google Scholar] [CrossRef] [PubMed]
- Lobbezoo, D.J.; van Kampen, R.J.; Voogd, A.C.; Dercksen, M.W.; van den Berkmortel, F.; Smilde, T.J.; van de Wouw, A.J.; Peters, F.P.; van Riel, J.M.; Peters, N.A.; et al. Prognosis of metastatic breast cancer subtypes: The hormone receptor/HER2-positive subtype is associated with the most favorable outcome. Breast Cancer Res. Treat. 2013, 141, 507–514. [Google Scholar] [CrossRef] [PubMed]
- Sundquist, M.; Brudin, L.; Tejler, G. Improved survival in metastatic breast cancer 1985–2016. Breast 2017, 31, 46–50. [Google Scholar] [CrossRef]
- Slamon, D.J.; Neven, P.; Chia, S.; Fasching, P.A.; de Laurentiis, M.; Im, S.A.; Petrakova, K.; Val Bianchi, G.; Esteva, F.J.; Martin, M.; et al. Overall survival with ribociclib plus fulvestrant in advanced breast cancer. N. Engl. J. Med. 2019, 382, 514–525. [Google Scholar] [CrossRef]
- Sledge, G.W., Jr.; Toi, M.; Neven, P.; Sohn, J.; Inoue, K.; Pivot, X.; Burdaeva, O.; Okera, M.; Masuda, N.; Kaufman, P.A.; et al. The effect of abemaciclib plus fulvestrant on overall survival in hormone receptor-positive, ERBB2-negative breast cancer that progressed on endocrine therapy-MONARCH 2: A randomized clinical trial. JAMA Oncol. 2019, 6, 116–124. [Google Scholar] [CrossRef]
- Swain, S.M.; Kim, S.B.; Cortes, J.; Ro, J.; Semiglazov, V.; Campone, M.; Ciruelos, E.; Ferrero, J.M.; Schneeweiss, A.; Knott, A.; et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): Overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013, 14, 461–471. [Google Scholar] [CrossRef] [Green Version]
- Cardona-Morrell, M.; Kim, J.; Turner, R.M.; Anstey, M.; Mitchell, I.A.; Hillman, K. Non-beneficial treatments in hospital at the end of life: A systematic review on extent of the problem. Int. J. Qual. Health Care 2016, 28, 456–469. [Google Scholar] [CrossRef]
- Ho, T.H.; Barbera, L.; Saskin, R.; Lu, H.; Neville, B.A.; Earle, C.C. Trends in the aggressiveness of end-of-life cancer care in the universal health care system of Ontario, Canada. J. Clin. Oncol. 2011, 29, 1587–1591. [Google Scholar] [CrossRef] [Green Version]
- Nappa, U.; Lindqvist, O.; Rasmussen, B.H.; Axelsson, B. Palliative chemotherapy during the last month of life. Ann Oncol. 2011, 22, 2375–2380. [Google Scholar] [CrossRef]
- Choi, Y.; Keam, B.; Kim, T.M.; Lee, S.H.; Kim, D.W.; Heo, D.S. Cancer treatment near the end-of-life becomes more aggressive: Changes in trend during 10 years at a single institute. Cancer Res. Treat. 2015, 47, 555–563. [Google Scholar] [CrossRef] [Green Version]
- Lee, H.S.; Chun, K.H.; Moon, D.; Yeon, H.K.; Lee, S.; Lee, S. Trends in receiving chemotherapy for advanced cancer patients at the end of life. BMC Palliat. Care 2015, 14, 4. [Google Scholar] [CrossRef] [Green Version]
- Prigerson, H.G.; Bao, Y.; Shah, M.A.; Paulk, M.E.; LeBlanc, T.W.; Schneider, B.J.; Garrido, M.M.; Reid, M.C.; Berlin, D.A.; Adelson, K.B.; et al. Chemotherapy use, performance status, and quality of life at the end of life. JAMA Oncol. 2015, 1, 778–784. [Google Scholar] [CrossRef] [PubMed]
- Anders, C.K.; Peppercorn, J. Treating in the dark: Unanswered questions on costs and benefits of late line therapy for metastatic breast cancer. Cancer Investig. 2009, 27, 13–16. [Google Scholar] [CrossRef] [PubMed]
- Lobbezoo, D.J.; van Kampen, R.J.; Voogd, A.C.; Dercksen, M.W.; van den Berkmortel, F.; Smilde, T.J.; van de Wouw, A.J.; Peters, F.P.; van Riel, J.M.; Peters, N.A.; et al. Prognosis of metastatic breast cancer: Are there differences between patients with de novo and recurrent metastatic breast cancer? Br. J. Cancer 2015, 112, 1445–1451. [Google Scholar] [CrossRef] [PubMed]
- Hui, D.; Nooruddin, Z.; Didwaniya, N.; Dev, R.; de la Cruz, M.; Kim, S.H.; Kwon, J.H.; Hutchins, R.; Liem, C.; Bruera, E. Concepts and definitions for “actively dying”, “end of life”, “terminally ill”, “terminal care”, and “transition of care”: A systematic review. J. Pain Symptom Manag. 2014, 47, 77–89. [Google Scholar] [CrossRef] [PubMed]
- Zorginstituut Nederland. Zinnige Zorg—Systematische Analyse Nieuwvormingen; Zorginstituut Nederland: Diemen, The Netherlands, 2015.
- Bestvina, C.M.; Wroblewski, K.E.; Daly, B.; Beach, B.; Chow, S.; Hantel, A.; Malec, M.; Huber, M.T.; Polite, B.N. A rules-based algorithm to prioritize poor prognosis cancer patients in need of advance care planning. J. Palliat Med. 2018, 21, 846–849. [Google Scholar] [CrossRef] [Green Version]
- Ferrario, A.; Xu, X.; Zhang, F.; Ross-Degnan, D.; Wharam, J.F.; Wagner, A.K. Intensity of end-of-life care in a cohort of commercially insured women with metastatic breast cancer in the United States. JCO Oncol. Pract. 2021, 17, e194–e203. [Google Scholar] [CrossRef]
- Tanguy-Melac, A.; Denis, P.; Fagot-Campagna, A.; Gastaldi-Menager, C.; Laurent, M.; Tuppin, P. Intensity of care, expenditure, and place of death in French Women in the year before their death from breast cancer: A population-based study. Cancer Control 2020, 27, 1073274820977175. [Google Scholar] [CrossRef]
- Wright, A.A.; Zhang, B.; Keating, N.L.; Weeks, J.C.; Prigerson, H.G. Associations between palliative chemotherapy and adult cancer patients’ end of life care and place of death: Prospective cohort study. BMJ 2014, 348, g1219. [Google Scholar] [CrossRef] [Green Version]
- Gomes, B.; Higginson, I.J.; Calanzani, N.; Cohen, J.; Deliens, L.; Daveson, B.A.; Bechinger-English, D.; Bausewein, C.; Ferreira, P.L.; Toscani, F.; et al. Preferences for place of death if faced with advanced cancer: A population survey in England, Flanders, Germany, Italy, The Netherlands, Portugal and Spain. Ann. Oncol. 2012, 23, 2006–2015. [Google Scholar] [CrossRef] [PubMed]
- Evans, N.; Pasman, H.R.; Vega Alonso, T.; van den Block, L.; Miccinesi, G.; van Casteren, V.; Donker, G.; Bertolissi, S.; Zurriaga, O.; Deliens, L.; et al. End-of-life decisions: A cross-national study of treatment preference discussions and surrogate decision-maker appointments. PLoS ONE 2013, 8, e57965. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Besseling, J.; Reitsma, J.; van Erkelens, J.A.; Schepens, M.H.J.; Siroen, M.P.C.; des Plantes, Z.C.M.P.; van Berge Henegouwen, M.I.; Beerepoot, L.V.; van Voorthuizen, T.; van Zuylen, L.; et al. Use of palliative chemotherapy and ICU admissions in gastric and esophageal cancer patients in the last phase of life: A Nationwide observational study. Cancers 2021, 13, 145. [Google Scholar] [CrossRef] [PubMed]
- Accordino, M.K.; Wright, J.D.; Vasan, S.; Neugut, A.I.; Gross, T.; Hillyer, G.C.; Hershman, D.L. Association between survival time with metastatic breast cancer and aggressive end-of-life care. Breast Cancer Res. Treat. 2017, 166, 549–558. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Karanth, S.; Rajan, S.S.; Sharma, G.; Yamal, J.M.; Morgan, R.O. Racial-ethnic disparities in end-of-life care quality among lung cancer patients: A SEER-Medicare-based study. J. Thorac. Oncol. 2018, 13, 1083–1093. [Google Scholar] [CrossRef] [Green Version]
- Soto-Perez-de-Celis, E.; Chavarri-Guerra, Y.; Pastrana, T.; Ruiz-Mendoza, R.; Bukowski, A.; Goss, P.E. End-of-life care in Latin America. J. Glob. Oncol. 2017, 3, 261–270. [Google Scholar] [CrossRef]
- Edman Kessler, L.; Sigfridsson, J.; Hatzidaki, D.; Bergh, J.; Foukakis, T.; Georgoulias, V.; Matikas, A. Chemotherapy use near the end-of-life in patients with metastatic breast cancer. Breast Cancer Res. Treat. 2020, 181, 645–651. [Google Scholar] [CrossRef]
- Mathew, A.; Achkar, T.; Abberbock, S.; Sandhu, G.S.; Jacob, M.E.; Villgran, V.D.; Rosenzweig, M.Q.; Puhalla, S.; Brufsky, A.M. Prevalence and determinants of end-of-life chemotherapy use in patients with metastatic breast cancer. Breast J. 2017, 23, 718–722. [Google Scholar] [CrossRef]
- Cartwright, C.; Onwuteaka-Philipsen, B.D.; Williams, G.; Faisst, K.; Mortier, F.; Nilstun, T.; Norup, M.; van der Heide, A.; Miccinesi, G. Physician discussions with terminally ill patients: A cross-national comparison. Palliat. Med. 2007, 21, 295–303. [Google Scholar] [CrossRef]
- Merchant, S.J.; Brogly, S.B.; Goldie, C.; Booth, C.M.; Nanji, S.; Patel, S.V.; Lajkosz, K.; Baxter, N.N. Palliative care is associated with reduced aggressive end-of-life care in patients with gastrointestinal cancer. Ann. Surg. Oncol. 2018, 25, 1478–1487. [Google Scholar] [CrossRef]
- Irvin, W., Jr.; Muss, H.B.; Mayer, D.K. Symptom management in metastatic breast cancer. Oncologist 2011, 16, 1203–1214. [Google Scholar] [CrossRef] [Green Version]
- Park, I.H.; Lee, K.S.; Ro, J. Effects of second and subsequent lines of chemotherapy for metastatic breast cancer. Clin. Breast Cancer 2015, 15, e55–e62. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schnipper, L.E.; Davidson, N.E.; Wollins, D.S.; Tyne, C.; Blayney, D.W.; Blum, D.; Dicker, A.P.; Ganz, P.A.; Hoverman, J.R.; Langdon, R.; et al. American society of clinical oncology statement: A conceptual framework to assess the value of cancer treatment options. J. Clin. Oncol. 2015, 33, 2563–2577. [Google Scholar] [CrossRef]
- Schnipper, L.E.; Smith, T.J.; Raghavan, D.; Blayney, D.W.; Ganz, P.A.; Mulvey, T.M.; Wollins, D.S. American society of clinical oncology identifies five key opportunities to improve care and reduce costs: The top five list for oncology. J. Clin. Oncol. 2012, 30, 1715–1724. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Milton, L.; Behroozian, T.; Coburn, N.; Trudeau, M.; Razvi, Y.; McKenzie, E.; Karam, I.; Lam, H.; Chow, E. Prediction of breast cancer-related outcomes with the Edmonton symptom assessment scale: A literature review. Support Care Cancer 2021, 29, 595–603. [Google Scholar] [CrossRef] [PubMed]
- Cardoso, F.; Costa, A.; Senkus, E.; Aapro, M.; Andre, F.; Barrios, C.H.; Bergh, J.; Bhattacharyya, G.; Biganzoli, L.; Cardoso, M.J.; et al. 3rd ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 3). Ann. Oncol. 2017, 28, 16–33. [Google Scholar] [CrossRef] [PubMed]
- Scibetta, C.; Kerr, K.; McGuire, J.; Rabow, M.W. The costs of waiting: Implications of the timing of palliative care consultation among a cohort of decedents at a comprehensive cancer center. J. Palliat. Med. 2016, 19, 69–75. [Google Scholar] [CrossRef]
Variation | All Patients | Patients who Died in Hospital | ||
---|---|---|---|---|
n = 203 | % | n = 50 | % | |
Gender | ||||
Female | 203 | 100% | 50 | 100% |
Male | 0 | 0% | 0 | 0% |
Incidence year ABC | ||||
2007–2009 | 81 | 40% | 20 | 40% |
2010–2013 | 93 | 46% | 24 | 48% |
2014–2017 | 29 | 14% | 6 | 12% |
Age at diagnosis ABC (years) | ||||
Median (range) | 63 | (28–90) | 63 | (28–87) |
<65 years | 105 | 52% | 28 | 56% |
65+ years | 98 | 48% | 22 | 44% |
Subtype | ||||
HR+/HER2− | 124 | 61% | 31 | 62% |
HR+/HER2+ | 29 | 14% | 6 | 12% |
HR−/HER2+ | 20 | 10% | 5 | 10% |
HR−/HER2− | 27 | 13% | 6 | 12% |
Unknown | 3 | 2% | 2 | 4% |
Metastatic-free interval | ||||
De novo (<3 months) | 53 | 26% | 17 | 34% |
3–24 months | 32 | 16% | 7 | 14% |
>24 months | 118 | 58% | 26 | 52% |
Systemic treatments given for ABC | ||||
Chemotherapy with or without targeted therapy | 130 | 64% | 37 | 74% |
Endocrine therapy with or without targeted therapy | 124 | 61% | 26 | 52% |
None | 21 | 10% | 5 | 10% |
Number of systemic treatment lines given | ||||
Median (range) | 2 | (0–10) | 2 | (0–8) |
0 | 21 | 10% | 5 | 10% |
1 | 54 | 27% | 18 | 36% |
2 | 31 | 15% | 7 | 14% |
3 | 23 | 11% | 5 | 10% |
4+ | 74 | 36% | 15 | 30% |
Final systemic treatment | ||||
Chemotherapy with or without targeted therapy | 109 | 54% | 32 | 64% |
Endocrine-targeted therapy | 13 | 6% | 12 | 24% |
Endocrine therapy | 54 | 26% | 0 | 0% |
Targeted therapy only | 6 | 3% | 1 | 2% |
No systemic therapy | 21 | 10% | 5 | 10% |
Performance status at start last treatment line | ||||
WHO 0–1 | 81 | 40% | 18 | 36% |
WHO 2–3 | 100 | 49% | 28 | 56% |
WHO 4 | 2 | 1% | 1 | 2% |
Unknown | 20 | 10% | 3 | 6% |
Cause of death | ||||
Breast cancer | 176 | 87% | 47 | 94% |
Progression of disease | 167 | 82% | 39 | 78% |
Complication of treatment for ABC | 9 | 4% | 8 | 16% |
Other | 13 | 6% | 3 | 6% |
Unknown | 14 | 7% | 0 | 0% |
Time between diagnosis ABC and death (years) | ||||
<1 | 76 | 37% | 21 | 42% |
1–3 | 97 | 48% | 28 | 56% |
≥4 | 30 | 15% | 1 | 2% |
Variation | n = 203 | % | ||
---|---|---|---|---|
Systemic treatment near end of life | ||||
New chemotherapy ≤30 days before death | 19 | 9% | ||
Ongoing chemotherapy ≤14 days before death | 42 | 21% | ||
Health care use within the last 6 months of life | ||||
ER-visit | 144 | 71% | ||
Hospital admission (reason) | 154 * | 76% | ||
Toxicity of systemic therapy | 18 | 12% | ||
Complication of other therapy | 6 | 4% | ||
Tumor related symptoms | 92 | 60% | ||
Other | 22 | 14% | ||
Unknown | 35 | 23% | ||
ICU-admission (reason) | 12 ** | 6% | ||
Toxicity of systemic therapy | 4 | 33% | ||
Complication of other therapy | 1 | 8% | ||
Tumor related symptoms | 6 | 50% | ||
Other | 1 | 8% | ||
Unknown | 3 | 25% | ||
CPR | 3 | 2% | ||
Mechanical ventilation | 10 | 5% | ||
Surgery | 9 | 4% | ||
Radiotherapy | 43 | 21% | ||
Place of death | ||||
Hospital (localization) | 50 | 25% | ||
General ward | 40 | 80% | ||
ICU or Medium care | 9 | 18% | ||
ER | 1 | 2% | ||
Hospice | 28 | 14% | ||
Rehabilitation | 5 | 3% | ||
Home | 107 | 53% | ||
Discharged from hospital, place unknown | 13 | 6% |
Characteristic | Category | Hospital Admission ≤6 Months of Life | Death in Hospital | ||
---|---|---|---|---|---|
Frequency | Multivariable | Frequency | Multivariable | ||
% | OR (95%CI)p-Value | % | OR (95%CI)p-Value | ||
Incidence year | 2007–2009 | 77 | reference | 24 | reference |
2010–2013 | 71 | 0.66 (0.30–1.49) | 25 | 1.49 (0.65–3.40) | |
2014–2017 | 86 | 1.45 (0.38–5.52) | 21 | 1.14 (0.37–3.84) | |
Age at diagnosis | <65 years | 84 | 3.12 (1.37–7.07) | 27 | 0.79 (0.34–1.71) |
65+ years | 67 | reference | 21 | reference | |
Subtype | HR+/HER2− | 75 | reference | 25 | reference |
HR+/HER2+ | 62 | 0.26 (0.09–0.76) ** | 21 | 0.59 (0.18–1.90) | |
HR−/HER2+ | 90 | 1.92 (0.37–9.92) | 25 | 1.15 (0.37–3.95) | |
TN | 85 | 1.21 (0.35–4.23) | 22 | 0.51 (0.14–1.81) | |
Metastatic-free interval | de novo | 89 | 4.41 (1.55–12.5) *** | 32 | 2.03 (0.88–4.72) |
3–24 months | 75 | 0.55 (0.19–1.63) | 22 | 0.92 (0.29–2.91) | |
>24 months | 70 | reference | 21 | reference | |
WHO performance status | 0–1 | 73 | reference | 20 | reference |
2–4 | 78 | 1.61 (0.76–3.41) | 27 | 1.56 (0.73–3.32) | |
Survival time | <1 year | 81 | 2.41 (0.97–5.99) * | 27 | 1.01 (0.43–2.37) |
≥1 year | 73 | reference | 23 | reference | |
New chemotherapy ≤30 days before death | No | 74 | reference | 18 | reference |
Yes | 95 | 3.70 (0.16–8.33) | 79 | 14.4 (2.85–73.0) *** | |
Ongoing chemotherapy ≤14 days before death | No | 71 | reference | 17 | reference |
Yes | 95 | 12.8 (1.38–120) *** | 50 | 2.05 (0.67–6.28) |
Characteristic | Category | New Chemotherapy ≤30 Days before Death | Ongoing Chemotherapy ≤14 Days before Death | ||
---|---|---|---|---|---|
Frequency | Multivariable | Frequency | Multivariable | ||
% | OR (95%CI)p-Value | % | OR (95%CI)p-Value | ||
Incidence year | 2007–2009 | 14 | reference | 22 | reference |
2010–2013 | 8 | 0.39 (0.13–1.19) | 20 | 0.81 (0.36–1.83) | |
2014–2017 | 3 | 0.13 (0.01–1.21) | 24 | 1.10 (0.35–3.43) | |
Age at diagnosis | <65 years | 16 | 11.8 (2.46–56.9) *** | 32 | 4.76 (2.04–11.1) *** |
65+ years | 2 | reference | 9 | reference | |
Subtype | HR+/HER2− | 8 | reference | 16 | reference |
HR+/HER2+ | 10 | 0.64 (0.14–2.87) | 24 | 1.17 (0.41–3.36) | |
HR−/HER2+ | 5 | 0.45 (0.05–4.08) | 15 | 0.71 (0.18–2.81) | |
TN | 19 | 1.58 (0.40–6.18) | 44 | 3.65 (1.36–9.80) ** | |
Metastatic-free interval | de novo | 9 | 1.24 (0.35–4.39) | 21 | 1.11 (0.46–2.69) |
3–24 months | 13 | 0.68 (0.16–2.91) | 22 | 0.66 (0.22–1.95) | |
>24 months | 9 | reference | 21 | reference | |
WHO performance status | 0–1 | 9 | reference | 18 | reference |
2–4 | 10 | 1.68 (0.56–4.99) | 24 | 1.50 (0.70–3.22) | |
Survival time | <1 year | 15 | 4.50 (1.40–14.5) *** | 24 | 1.49 (0.66–3.40) |
≥1 year | 6 | reference | 19 | reference |
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Schmitz, R.S.J.M.; Geurts, S.M.E.; Ibragimova, K.I.E.; Tilli, D.J.P.; Tjan-Heijnen, V.C.G.; de Boer, M. Healthcare Use during the Last Six Months of Life in Patients with Advanced Breast Cancer. Cancers 2021, 13, 5271. https://doi.org/10.3390/cancers13215271
Schmitz RSJM, Geurts SME, Ibragimova KIE, Tilli DJP, Tjan-Heijnen VCG, de Boer M. Healthcare Use during the Last Six Months of Life in Patients with Advanced Breast Cancer. Cancers. 2021; 13(21):5271. https://doi.org/10.3390/cancers13215271
Chicago/Turabian StyleSchmitz, Renée. S. J. M., Sandra. M. E. Geurts, Khava. I. E. Ibragimova, Dominique. J. P. Tilli, Vivianne. C. G. Tjan-Heijnen, and Maaike de Boer. 2021. "Healthcare Use during the Last Six Months of Life in Patients with Advanced Breast Cancer" Cancers 13, no. 21: 5271. https://doi.org/10.3390/cancers13215271